This invention relates to the treatment of hyperhidrosis, ichthyosis, and wrinkling of the skin. In particular, this invention is directed toward conditions involving hyperactivity of the adnexa and the epidermis, excessive cellular aggregation within the epidermis and stratum corneum, and photoaging or dermatoheliosis.
The present invention resides in the discovery that certain mono- and dicarboxylic acids and their esters are effective in the treatment of these conditions, and represents a departure from the types of skin conditions on which such acids have previously been effective.
U.S. Pat. Nos. 4,292,326 (Nazarro-Porro, Sept. 29, 1981) and 4,386,104 (Nazarro-Porro, May 31, 1983) disclose the use of dicarboxylic acids in the treatment of acne and melanocytic hyperpigmentary dermatoses.
Emotional hyperhidrosis, which is the most common form of hyperhidrosis, is a noninflammatory exaggerated sweating response that comprises one socially or at work. The eccrine sweat glands of the axilla and volar aspects, palms and soles, are most often affected. Occasionally, the response is seen on the upper lip or forehead. Localized areas of involvement outside of the axillae and volar aspects are often referred to as an eccrine nevus. Axillary and volar hyperhidrosis may coexist in a given patient, but usually one site predominates and requires therapy.
Axillary hyperhidrosis may be quite mild and controlled by frequent use of antiperspirants. Volar hyperhidrosis often begins in infancy or childhood while the axillary type begins between 15 and 18 years of age. Current therapies are usually discouraging due to poor results and/or significant side effects.
Volar hyperhidrosis therapy includes two topical agents and systemic anticholinergics that have no effect on the axillary type. Topical formaldehyde is limited by being a common allergic sensitizer while topical glutaraldehyde produces a brownish stain. Systemic cholinergic agents like Robinul (a trade name for glycopyrrolate, a known anticholinergic available from A.H. Robins Company, Pharmaceutical Division, Richmond, Va.) are occasionally helpful but usually produce unpleasant side effects at therapeutic doses.
Two topical products are generally effective in both types of hyperhidrosis. Topical aluminum chloride hexahydrate has been linked to Parkinson's and Alzheimer's diseases. Ionopharesis is reasonably effective but requires cumbersome electrical ion exchange machines. Sympathectomy is a very aggressive surgical procedure effective to some degree in both types but presenting a very high risk. Selective surgical excision of overactive axillary sweat glands is often successful but most patients are reluctant to have such a procedure performed.
Ichthyosis vulgaris, the most common of the ichthyoses, is the most common disorder of keratinization. It usually starts in childhood and is characterized by "fish scales" and keratosis pilaris most prominent on the extremities. Other common findings include scaling of the lower back and abdomen with hyperkeratosis of the feet. This disorder results from excessive aggregation of keratinocytes. Current lifelong therapy consists of emollients, including most standard ones which are poorly effective, and alpha hydroxy acids which may produce burning sensations, especially in children. Propylene glycol, a common allergic sensitizer and irritant, is also reported to be effective, but has obvious disadvantages. Alpha hydroxy acids are distinct chemically from dicarboxylic acids in that they are short chain (3 to 5 carbon) compounds without an associated mono-, di-, or tricarboxylic moiety at either end.
Keratosis pilaris, generally considered to be a local follicular subset of ichthyosis vulgaris, consists of a horny plug containing inspissated sebrum and epithelial cells with a coiled hair filling the follicular infundibulum usually on the proximal extremities. The majority of atopic individuals and those afflicted with ichthyosis vulgaris display keratosis pilaris. The current treatment regimens utilizing emollients, keratolytics, and tretinoin are often disappointing despite prolonged treatment.
Wrinkling of the skin results from a combination of intrinsic thinning and photoaging (dermatoheliosis), with the latter being the primary cause. One compound, transretinoic acid, has been proven to reverse such structural damage with topical application.
These are examples of conditions for which it has been discovered that dicarboxylic acids within the scope of the present invention are an effective treatment when applied topically. In general, the invention applies to adnexal and epidermal hyperactive production and excessive epidermal aggregation disease states such as hyperhidrosis and the ichthyoses.